Consent Builder: an innovative tool for creating research informed consent documents.

Objective: To describe process innovations related to research informed consent documents, and development and formative evaluation of Consent Builder, a platform for generating consent documents for multicenter studies. Materials and Methods: Analysis of Institutional Review Board workflows and documents, followed by process redesign, document redesign, and software development. Locally developed software leverages REDCap and LaTeX. A small-scale usability study was conducted. Results: Process innovations were combining document types, and conceptualizing 2-part informed consent documents: part 1 standardizing the study description and part 2 with local site verbiage. Consent Builder was implemented in the Trial Innovation Network. User survey scores were acceptable; but areas for improvement were noted. LaTeX coding was the biggest challenge for users. Discussion: The process changes were generally well accepted. The software implementation uncovered un-accounted for assumptions, and variability in IRB review workflow across centers. Technical modifications may be needed before widespread implementation. Conclusion: We demonstrated proof-of-concept of an approach to generate research consent documents that are consistent across sites in study description, but which allow for customization of local site verbiage. The Consent Builder tool is an example of an operational innovation, helping meet a need that arose in part due to regulations around use of Single IRB for multicenter trials.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

Retrospective statistical analysis of lyophilized protein formulations of progenipoietin using PLS: determination of the critical parameters for long-term storage stability.

Although certain criteria have become recognized as being essential for a stable lyophilized formulation, the relative importance of different stability criteria has not been demonstrated quantitatively. This study uses multivariate statistical methods to determine the relative importance of certain formulation variables that affect long-term storage stability of a therapeutic protein. Using the projection to latent structures (PLS) method, a retrospective analysis was conducted of 18 formulations of progenipoietin (ProGP), a potential protein therapeutic agent. The relative importance of composition, pH, maintenance of protein structure (as determined by infrared (IR) spectroscopy), and thermochemical properties of the glassy state (as measured by differential scanning calorimetry (DSC)) were evaluated. Various stability endpoints were assessed and validated models constructed for each using the PLS method. Retention of parent protein and the appearance of degradation products could be adequately modeled using PLS. The models demonstrate the importance of retention of native structure in the solid state and controlling the pH. The relative importance of T(g) in affecting storage stability was low, as all of the samples had T(g) values above the highest storage temperature (40 degrees C). However, other indicators of molecular mobility in the solid state, such as change in DeltaC(p) upon annealing, appear to be important, even for storage below T(g). For the first time, the relative importance of certain properties in controlling long-term storage stability could be assessed quantitatively. In general, the most important parameters appear to be pH and retention of native structure in the solid state. However, for some stability endpoints, the composition (concentration of protein or various excipients), as well as some DSC parameters, were found to be significant in predicting long-term stability.